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SNCTP000003557 | NCT03744910 | BASEC2019-01145

Studie zur Bewertung der Wirksamkeit und Sicherheit der Behandlung des Prüfmedikaments Clazakizumab im Vergleich zu einem Placebo (inaktive Substanz) bei Empfängern von Nierentransplantationen mit chronisch aktiver Antikörper-vermittelter Abstoßung (CABMR)

Data source: BASEC (Imported from 07.08.2020), WHO (Imported from 02.08.2020)
Changed: 02.08.2020
Disease category: Other

Brief description of trial (Data source: BASEC)

Ziel dieser Studie ist es, die Wirksamkeit und Sicherheit der Behandlung mit Clazakizumab im Vergleich zu einem Placebo (inaktive Substanz) bei Empfängern von Nierentransplantationen mit CABMR zu untersuchen. In der Studie wird untersucht, ob Clazakizumab den Funktionsverlust der transplantierten Niere verlangsamen oder verhindern und den Zeitraum verlängern kann, bevor die Patienten wieder zur Dialyse gehen oder eine neue Niere bekommen müssen.

Clazakizumab oder das Placebo wird alle 4 Wochen subkutan (Injektionen unter die Haut) verabreicht.

Die Studie wird aus folgenden Behandlungsperioden bestehen:
- Das Screening-Verfahren beträgt bis zu 6 Wochen. Der Screening-Besuch besteht aus einer Bewertung, um festzustellen, ob die Patienten alle Zulassungsvoraussetzungen für die Teilnahme an der Studie erfüllen.
- Die Behandlungsdauer beträgt bis zu 260 Wochen, wobei die Patienten alle 4 Wochen eine subkutane Injektion (entweder Clazakizumab 12,5 mg / ml oder Placebo 1 ml) erhalten.
- Die Nachbeobachtungszeit beträgt bis zu 5 Monaten nach der letzten Dosis des Prüfpräparats.
Die maximale Studiendauer für einen einzelnen Patienten beträgt ca. 5,5 Jahre.

Health conditions investigated (Data source: BASEC)

Behandlung einer chronisch aktiven Antikörper-vermittelten Abstoßung bei Patienten mit Nierentransplantationen

Health conditions (Data source: WHO)

Antibody-mediated Rejection

Rare disease (Data source: BASEC)

No

Intervention investigated (e.g. drug, therapy or campaign) (Data source: BASEC)

Die Patienten werden nach dem Zufallsprinzip ausgewählt und erhalten entweder:
Clazakizumab 12,5 mg / ml SC-Injektion einmal alle 4 Wochen für bis zu 260 Wochen oder bis zum Verlust des Allotransplantats oder Tod
oder
- Placebo-1-ml-SC-Injektion alle 4 Wochen bis zu 260 Wochen oder bis zum Verlust des Allotransplantats oder Tod
- Die Patienten müssen auch eine prophylaktische Behandlung (orales Trimethoprim / Sulfamethoxazol 80 mg als Trimethoprim täglich oder 160 mg als Trimethoprim x 3 pro Woche) für PJP (Pneumocystis jiroveci pneumonia) vom Screening-Termin bis einschließlich Woche 52 einnehmen alternative prophylaktische PJP-Therapie beim Screening Sie können nach Ermessen des Prüfarztes verbleiben oder wenn die derzeitige Therapie nicht geeignet ist, sollte Trimethoprim / Sulfamethoxazol mindestens 1 Woche vor V2 begonnen werden. Für den Rest der Studie (> Woche 52) sollte die PJP-Prophylaxe nach Ermessen des Prüfarztes fortgesetzt werden.

Interventions (Data source: WHO)

Biological: Clazakizumab;Drug: Normal saline

Criteria for participation in trial (Data source: BASEC)

1. Alter 18-70 Jahre
2. Empfänger von Lebendspender- / verstorbenen Spendernierentransplantaten ≥ 6 Monate ab dem Zeitpunkt
der Transplantation
3. Diagnose von CABMR (gemäß den diagnostischen Kriterien von Banff 2015)

Exclusion criteria (Data source: BASEC)

1. eGFR <25 mL/min/1.73 m2 or >65 mL/min/1.73 m2 (MDRD4)
2. Vorgeschichte von Magen - Darm - Perforationen, Divertikelerkrankungen oder Divertikulitis oder entzündliche Darmerkrankung
3. Aktive Infektionen, die systemische antimikrobielle Wirkstoffe erfordern und sind ungelöst vor dem Screening

Inclusion/Exclusion Criteria (Data source: WHO)


Unless specified otherwise, all eligibility criteria time-intervals are assessed with
respect to the screening visit. In order to be eligible to participate in the trial, a
subject must meet all of the following inclusion criteria:

1. Age 18-70 years.

2. Living donor/deceased donor kidney transplant recipients =6 months from time of
transplant.

3. Diagnosis of CABMR (according to Banff 2015 diagnostic criteria) to include all of the
following:

- Biopsy-proven CABMR (i.e., chronic glomerulopathy (cg) >0) with/without C4d
staining. Repeat biopsy to be performed if previous biopsy is not within 6 months
(+3 weeks) of the start of the screening period. The local pathologist's
diagnosis will be reviewed by a central pathologist to confirm eligibility for
entry into the study. Subjects without evidence of chronic tissue injury on light
microscopy but who have glomerular basement membrane double contours on electron
microscopy (cg1a) are eligible.

- Positive for HLA DSA (using single-antigen bead-based assays) post-transplant.
Local laboratory DSA results will be reviewed by the central HLA reviewer to
confirm eligibility for entry into the study. If presence of HLA DSA is confirmed
within 6 months (+3 weeks) of the start of the screening period, the test does
not need to be repeated for eligibility.

- Note: Treatments for ABMR (including CABMR) or TCMR are not allowed within 3
months of the start of screening (see Exclusion Criterion 3). If subject has
received one of these treatments at any time prior, a repeat biopsy and repeat
DSA test must be performed after halting/completing treatment (to show continuing
CABMR). At least 2 months ± 2 weeks should elapse from the end of treatment
before the repeat biopsy and DSA test can be performed.

4. Written informed consent obtained from subject (or legally acceptable representative)
before any trial-related procedures.

Unless specified otherwise, all exclusion criteria time-intervals are assessed with respect
to the screening visit. A subject is not eligible if any exclusion criteria are met:

1. Participant is unable or unwilling to comply with study procedures in the opinion of
the Investigator.

2. Multi-organ transplant recipient or cell transplant (islet, bone marrow, stem cell)
recipient. Note: recipients of multiple previous kidney transplants are allowed.

3. Treatment for ABMR (including CABMR) or TCMR within 3 months of the start of
screening.

4. Received T cell depleting agents (e.g., alemtuzumab, anti-thymocyte globulin) within 3
months of the start of screening.

5. Treatment with mTOR inhibitors within 4 weeks of the start of screening.

6. Biopsy showing pure TCMR or advanced interstitial fibrosis (ci3), advanced tubular
atrophy (ct3), vascular fibrous intimal thickening (cv3) or other significant causes
of renal dysfunction (e.g., BKV nephropathy, glomerulonephritis).

7. Impaired renal function due to disorders in the transplanted allograft (e.g., renal
artery stenosis, hydronephrosis).

8. eGFR <25 mL/min/1.73 m2 or >65 mL/min/1.73 m2 (MDRD4).

9. Nephrotic range proteinuria defined as spot urine albumin creatinine ratio (UACR)
=2,200 mg/g (=220 mg/mmol). If spot UACR is above defined limits, repeat test on
separate day to confirm ineligibility (or collect 24-hour urine to confirm nephrotic
range proteinuria (=3.0 g/day)).

10. Pregnant, breastfeeding, or unwillingness to practice adequate contraception (i.e., a
highly effective or acceptable method of contraception) during the study and for 5
months after last dose of investigational drug.

11. History of anaphylaxis or known hypersensitivity to clazakizumab or to any constituent
of the drug product.

12. Abnormal LFTs (alanine aminotransferase (ALT)/aspartate aminotransferase
(AST)/bilirubin >1.5 x upper limit of normal) or other significant liver disease.

13. History of active tuberculosis (TB).

14. History of latent TB (e.g., positive QuantiFERON-TB test) without history of active TB
unless subject has completed a full course of prophylactic treatment.

15. History of human immunodeficiency virus (HIV) infection or positive for HIV.

16. Seropositive for hepatitis B surface antigen (HBsAg).

17. Hepatitis C virus (HCV) RNA positive.

18. Known EBV mismatch (at time of transplant): donor seropositive, recipient
seronegative.

19. History of GI perforation; diverticular disease or diverticulitis (except if disease
has been fully excised); or inflammatory bowel disease (except fully excised
ulcerative colitis).

20. Neutropenia (<1,000/mm3) or thrombocytopenia (<50,000/mm3).

21. Active infections requiring systemic antimicrobial agents and unresolved prior to
screening.

22. History of or current invasive fungal infection or other opportunistic infection,
including (but not limited to) the following: a nontuberculous mycobacterial
infection, aspergillosis, pneumocystosis, and toxoplasmosis.

23. Active viral infections such as BKV, CMV, or EBV based on polymerase chain reaction
(PCR) testing. Active infection is defined as a test result = lower limit of
quantification (LLOQ).

24. Current or recent (within 3 months) participation in an interventional trial.

25. Administration of a live vaccine within 6 weeks of the start of screening, including
but not limited to the following:

- Adenovirus

- Measles, mumps, and rubella

- Oral polio

- Oral typhoid

- Rotavirus

- Varicella zoster

- Yellow fever

26. History of alcohol or illicit substance (including marijuana) abuse.

27. Present or previous (within 3 years) malignancy except for basal cell carcinoma, fully
excised squamous cell carcinoma of the skin, or non-recurrent (within 5 years)
cervical carcinoma in-situ.

28. Presence of a condition or abnormality (i.e., clinically significant endocrine,
autoimmune, metabolic, neurological, psychiatric/psychological, renal, GI, hepatic,
and hematological or any other system abnormalities that are uncontrolled with
standard treatment) that in the opinion of the Investigator would compromise the
safety or life expectancy of the patient or the quality of the data.

29. History of intolerance to trimethoprim and/or sulfamethoxazole. This criterion does
not apply if subject is already

Further information on the trial in WHO primary registry

https://clinicaltrials.gov/show/NCT03744910

Further information on the trial from WHO database (ICTRP)

http://apps.who.int/trialsearch/Trial2.aspx?TrialID=NCT03744910

Further information on trial

Date trial registered

06.11.2018

Incorporation of the first participant

14.10.2019

Recruitment status

Recruiting

Academic title (Data source: WHO)

A Pivotal Phase 3 Trial to Evaluate the Safety and Efficacy of Clazakizumab for the Treatment of Chronic Active Antibody-mediated Rejection in Kidney Transplant Recipients

Type of trial (Data source: WHO)

Interventional

Design of the trial (Data source: WHO)

Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).

Phase (Data source: WHO)

Phase 3

Primary end point (Data source: WHO)

Incidence of all cause composite allograft loss

Contact information (Data source: WHO)

Please refer to primary and secondary sponsors

Trial results (Data source: WHO)

Results summary

no information available yet

Link to the results in the primary register

no information available yet

Information on the availability of individual participant data

no information available yet

Trial sites

Trial sites in Switzerland (Data source: BASEC)

Zurich

Countries (Data source: WHO)

Switzerland might not appear as site of trial if it has not yet been entered as such in the WHO primary registry.
Australia, Canada, Czechia, France, Germany, Hungary, Netherlands, Spain, United States

Contact for further information on the trial

Details of contact in Switzerland (Data source: BASEC)

Prof. Dr. Thomas Müller
+41 44 255 27 75
Thomas.Mueller@usz.ch

Contact for general information (Data source: WHO)

Study Director;Trial Registration Coordinator
CSL Behring
610-878-4000
clinicaltrials@cslbehring.com

Contact for scientific information (Data source: WHO)

Study Director;Trial Registration Coordinator
CSL Behring
610-878-4000
clinicaltrials@cslbehring.com

Principal Sponsor/Investigator

Principal sponsor (Data source: WHO)

CSL Behring

Additional sponsors (Data source: WHO)

ICON Clinical Research

Authorisation by the ethics committee (Data source: BASEC)

Name of the authorising ethics committee (for multicentre studies only the lead committee)

Kantonale Ethikkommission Zürich

Date of authorisation by the ethics committee

03.12.2019

Further trial identification numbers

Trial identification number of the ethics committee (BASEC-ID) (Data source: BASEC)

2019-01145

Secondary ID (Data source: WHO)

CSL300_3001 (VKTX01)